Increased platelet activating factor production in T.cruzi infected endothelial cells

The primary cause of myocarditis Worldwide is T. cruzi infection, a disease characterized by progressive inflammation associated with inflammatory cell migration. Transendothelial cell migration of inflammatory cells is dependent on the interaction of endothelial cell surface expression of platelet‐activating factor (PAF) with the PAF receptor expressed on inflammatory cells. We hypothesized that activation of human coronary artery endothelial cell (HCAEC) calcium‐independent phospholipase A 2 (iPLA 2 ) by T. cruzi would result in increased PAF production. We infected HCAEC with T. cruzi (multiplicity of infection, MOI 0.2) and measured the resultant PAF production. An increase in PAF was observed at 24 hrs (1143 ± 111 to 4360 ± 90 dpm, p<0.05, n=4) that was inhibited by pretreatment with ( S )‐BEL (0.5 μM, 10 minutes) to selectively inhibit iPLA 2 β (197 ± 22 dpm, p<0.05, n=4). Cardiac endothelial cells from wild type (WT) and iPLA 2 γ knockout (KO) mice showed similar increases in PAF production following T.cruzi infection. T. cruzi ‐infected iPLA 2 β‐KO cardiac endothelial cells demonstrated no significant increase in PAF production when compared to uninfected controls. Taken together, these results indicate that T.cruzi infection of HCAEC activates iPLA 2 β, resulting in increased PAF production. This may contribute to the recruitment of inflammatory cells to the myocardium that is seen in Chagas' disease.